George Moxley received the MD degree in 1976 from Washington University, St. Louis. After three years of residency and one year of chief residency in internal medicine, he has trained as a fellow and now as an assistant professor of rheumatology, first with a year of intensive clinical exposure followed by what will be five years of laboratory work with Dr. Shaun Ruddy. He has developed enzyme-linked immunoassays to identify monoclonal antibodies which he has produced by somatic cell hybridization and that are directed toward complement proteins. He has found by radioimmunoassay striking elevations of C3 anaphylatoxins in synovial fluids of patients with rheumatoid arthritis (RA) and acute gouty arthritis. The hypothesis to be examined in this proposal is that patients with RA produce rheumatoid factors (RFs) with cross-reactive idiotypes which are disease related and distinct from such immunoglobulins in RF-positive individuals with diseases other than RA. Substantial progress has been made toward the analysis. The applicant has developed techniques for preparing single cell suspensions of lymphocytes from rheumatoid synovial tissue, transforming B lymphocytes with Epstein-Barr virus, and analyzing culture supernatants for human immunoglobulin or RFs. He has produced antisera directed toward a synthetic peptide representing an important part of a monoclonal RF. He has synthesized oligonucleotides complementary to important parts of RF light chain genes and used them for hybridization to Southern blots of patients with rheumatoid arthritis (RA) or normals. The proposed research will compare immunoglobulin genes among rheumatoid synovium and cells of RF-positive individuals with diseases other than RA by means of hybridization with synthetic oligonucleotides; and the primary structure of immunoglobulins will be compared among rheumatoid synovial fluids or sera of RF-positive individuals lacking RA by immunoblotting with an antipeptide antiserum.